%0 Journal Article %T Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study %+ Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11) %+ Département d'Hématologie Clinique [CHU Nantes] %+ Site de Recherche Intégrée sur le Cancer - SIRIC « ILIAD » [Nantes] (INCA-DGOS-Inserm) %+ Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037) %+ Hôpital Haut-Lévêque [CHU Bordeaux] %+ Service d'hématologie biologique %+ Institut Mondor de Recherche Biomédicale (IMRB) %+ Service d'hématologie [Tours] %+ Centre hospitalier universitaire de Nantes (CHU Nantes) %+ Service d'Hématologie Clinique (CHU de Dijon) %+ Universitaire Ziekenhuizen Leuven %+ Laboratoire de Biochimie [Nantes] %+ CIC CHU ( Lille)/inserm %+ Hôpital JeanMinjoz %+ CHU Saint-Antoine [AP-HP] %+ Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS) %+ Service d'Hématologie [Institut Curie] %+ Service de biostatistiques et information médicale [Saint-Louis] %+ Hôpital de la Milétrie %+ Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND) %+ Hôpital Universitaire de Caen %+ Intergroupe francophone du myélome (IFM) %+ Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois] %+ Service d'Hématologie [CHRU Nancy] %+ Service d’Hématologie [Institut Paoli Calmettes, Marseille] %+ Département d'hématologie et de biologie [CHU Nantes] %+ Amsterdam UMC - Amsterdam University Medical Center %+ Service d'Hématologie %+ Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10) %+ Service de Médecine Onco-hématologie [La Roche sur Yon] %+ Service clinique des Maladies du Sang %+ Institut Jules Bordet [Bruxelles] %+ Service d'hématologie adulte [Hôpital de Saint Louis] %+ CHU Pontchaillou [Rennes] %+ CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato) %+ Hôpital Saint-Quentin %+ Centre de Recherches en Cancérologie de Toulouse (CRCT) %+ Erasmus University Medical Center [Rotterdam] (Erasmus MC) %A Moreau, Philippe %A Attal, Michel %A Hulin, Cyrille %A Arnulf, Bertrand %A Belhadj, Karim %A Benboubker, Lotfi %A Bene, Marie C. %A Broijl, Annemiek %A Caillon, Helene %A Caillot, Denis %A Corre, Jill %A Delforge, Michel %A Dejoie, Thomas %A Doyen, Chantal %A Facon, Thierry %A Sonntag, Cecile %A Fontan, Jean %A Garderet, Laurent %A Jie, Kon-Siong %A Karlin, Lionel %A Kuhnowski, Frederique %A Lambert, Jerome %A Leleu, Xavier %A Lenain, Pascal %A Macro, Margaret %A Mathiot, Claire %A Orsini-Piocelle, Frederique %A Perrot, Aurore %A Stoppa, Anne-Marie %A Donk, Niels W. C. J., van De %A Wuilleme, Soraya %A Zweegman, Sonja %A Kolb, Brigitte %A Touzeau, Cyrille %A Roussel, Murielle %A Tiab, Mourad %A Marolleau, Jean-Pierre %A Meuleman, Nathalie %A Vekemans, Marie-Christiane %A Westerman, Matthijs %A Klein, Saskia K. %A Levin, Mark-David %A Fermand, Jean Paul %A Escoffre-Barbe, Martine %A Eveillard, Jean-Richard %A Garidi, Reda %A Ahmadi, Tahamtan %A Zhuang, Sen %A Chiu, Christopher %A Pei, Lixia %A Boer, Carla, De %A Smith, Elena %A Deraedt, William %A Kampfenkel, Tobias %A Schecter, Jordan %A Vermeulen, Jessica %A Avet-Loiseau, Herve %A Sonneveld, Pieter %< avec comité de lecture %@ 0140-6736 %J The Lancet %I Elsevier %V 394 %N 10192 %P 29-38 %8 2019 %D 2019 %R 10.1016/S0140-6736(19)31240-1 %Z Life Sciences [q-bio]Journal articles %X Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1.60, 95% CI 1.21-2.12, p=0.0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10(-5) sensitivity threshold, assessed by multiparametric flow cytometry; both p<0.0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0.47, 95% CI 0 . 33-0.67, p<0.0001). 46 deaths on study were observed (14 vs 32, 0.43, 95% CI 0.23-0.80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma. Copyright (C) 2019 Elsevier Ltd. All rights reserved. %G English %L hal-03605015 %U https://u-picardie.hal.science/hal-03605015 %~ UNIV-PARIS7 %~ UNIV-NANTES %~ HCL %~ UNIV-TLSE3 %~ CNRS %~ UNIV-ANGERS %~ APHP %~ LORIA2 %~ CHLS %~ FNCLCC %~ CURIE %~ PAOLI_CALMETTES %~ IMRB %~ UPEC %~ HL %~ COMUE-NORMANDIE %~ PSL %~ USPC %~ CRCINA %~ UNIROUEN %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ SU-MED %~ GPMCND %~ UNIV-PARIS %~ INSTITUT-CURIE-PSL %~ SU-TI %~ U-PICARDIE %~ HEMATIM %~ ALLIANCE-SU %~ NANTES-UNIVERSITE %~ UNIV-NANTES-AV2022 %~ UNIV-UT3 %~ UT3-INP %~ UT3-TOULOUSEINP %~ TEST3-HALCNRS %~ CRCT